1. An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease
- Author
-
Peng, Yanchun, Felce, Suet Ling, Dong, Danning, Penkava, Frank, Mentzer, Alexander J, Yao, Xuan, Liu, Guihai, Yin, Zixi, Chen, Ji-Li, Lu, Yongxu, Wellington, Dannielle, Wing, Peter AC, Dominey-Foy, Delaney CC, Jin, Chen, Wang, Wenbo, Hamid, Megat Abd, Fernandes, Ricardo A, Wang, Beibei, Fries, Anastasia, Zhuang, Xiaodong, Ashley, Neil, Rostron, Timothy, Waugh, Craig, Sopp, Paul, Hublitz, Philip, Beveridge, Ryan, Tan, Tiong Kit, Dold, Christina, Kwok, Andrew J, Rich-Griffin, Charlotte, Dejnirattisa, Wanwisa, Liu, Chang, Kurupati, Prathiba, Nassiri, Isar, Watson, Robert A, Tong, Orion, Taylor, Chelsea A, Kumar Sharma, Piyush, Sun, Bo, Curion, Fabiola, Revale, Santiago, Garner, Lucy C, Jansen, Kathrin, Ferreira, Ricardo C, Attar, Moustafa, Fry, Jeremy W, Russell, Rebecca A, COMBAT Consortium, Stauss, Hans J, James, William, Townsend, Alain, Ho, Ling-Pei, Klenerman, Paul, Mongkolsapaya, Juthathip, Screaton, Gavin R, Dendrou, Calliope, Sansom, Stephen N, Bashford-Rogers, Rachael, Chain, Benny, Smith, Geoffrey L, McKeating, Jane A, Fairfax, Benjamin P, Bowness, Paul, McMichael, Andrew J, Ogg, Graham, Knight, Julian C, Dong, Tao, Peng, Yanchun [0000-0003-2340-0499], Penkava, Frank [0000-0001-9163-8576], Mentzer, Alexander J [0000-0002-4502-2209], Yin, Zixi [0000-0002-2044-5838], Wing, Peter AC [0000-0002-2354-3281], Fries, Anastasia [0000-0003-1609-5991], Zhuang, Xiaodong [0000-0002-6870-9003], Hublitz, Philip [0000-0001-8810-3247], Tan, Tiong Kit [0000-0001-8746-8308], Kwok, Andrew J [0000-0001-8928-5054], Rich-Griffin, Charlotte [0000-0001-8212-9542], Tong, Orion [0000-0002-0659-5944], Kumar Sharma, Piyush [0000-0002-6247-3503], Sun, Bo [0000-0002-5507-6657], Garner, Lucy C [0000-0002-6461-252X], Jansen, Kathrin [0000-0002-3803-7680], Attar, Moustafa [0000-0003-4116-1276], Fry, Jeremy W [0000-0003-3689-6606], Russell, Rebecca A [0000-0002-6517-6483], Stauss, Hans J [0000-0003-4340-7911], James, William [0000-0002-2506-1198], Klenerman, Paul [0000-0003-4307-9161], Mongkolsapaya, Juthathip [0000-0003-3416-9480], Screaton, Gavin R [0000-0002-3549-4309], Sansom, Stephen N [0000-0003-4569-8513], Bashford-Rogers, Rachael [0000-0002-6838-0711], Chain, Benny [0000-0002-7417-3970], Smith, Geoffrey L [0000-0002-3730-9955], Bowness, Paul [0000-0003-4597-0484], Dong, Tao [0000-0003-3545-3758], and Apollo - University of Cambridge Repository
- Subjects
Male ,Immunodominant Epitopes ,SARS-CoV-2 ,Gene Expression Profiling ,Antibody Affinity ,Receptors, Antigen, T-Cell ,COVID-19 ,Vaccinia virus ,Middle Aged ,Nucleocapsid Proteins ,Antibodies, Viral ,Severity of Illness Index ,humanities ,HLA-B7 Antigen ,Humans ,Female ,Amino Acid Sequence ,Immunologic Memory ,Aged ,Cell Line, Transformed ,T-Lymphocytes, Cytotoxic - Abstract
Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265, Funder: Chinese Academy of Medical Sciences (CAMS); doi: https://doi.org/10.13039/501100005150, Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440, NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.
- Published
- 2022